This is a revised competing continuation application designed to follow-up on the major findings from our initial funding period and to investigate the cognitive and motivational mechanisms underlying behavioral disinhibition in early onset alcohol dependence (AD) and related co-morbid externalizing (EXT) and internalizing disorders. AD is a heterogeneous disorder with considerable variation in severity of symptoms, types and severity of co- morbid disorders, age of onset, and course. Research indicates a strong association between AD and various disinhibitory phenotypes, such as co-morbid EXT disorders, impulsive personality traits, and laboratory measures of behavioral disinhibition, which are associated with an early onset, more severe symptoms, and chronic course. However, much remains to be learned about the processes that contribute to, and explain the, (i) heterogeneity and co-morbidity in AD, and (ii) the specific mechanisms underlying behavioral disinhibition in AD and related EXT disorders. Several mechanisms contribute to behavioral disinhibition, yet we know little about how: 1. specific cognitive and motivational processes interact to affect poor decision-making, behavioral undercontrol, and specific decisions to drink in those with alcohol dependence, and 2. how these processes vary as a function of co-morbid psychopathology. Many studies of disinhibitory processes in AD are associational in nature, which limits our understanding of the specific mechanisms that contribute to self- regulatory deficits in those with AD. The proposed study uses a dimensional} factorial design to examine the impact of manipulating working memory load and reward magnitude on decision-making and behavioral inhibition in those with AD and EXT disorders. Utilizing manipulations of working memory load and reward magnitude is a more powerful approach to identifying the manner in which working memory, reward sensitivity, and punishment sensitivity interact and contribute to AD and EXT. The first aim of this study is to use a dimensional model design to investigate disinhibitory processes associated with heterogeneity and co- morbidity of EXT in AD. The second aim is to more directly investigate the cognitive and motivational mechanisms underlying behavioral inhibition deficits in AD / EXT by directly manipulating WM load and magnitude of reward on different laboratory tasks. The third aim is to more directly assess the motivational /disinhibitory factors that influence decisions to drink in those with AD, and other EXT disorders. This study will build upon our knowledge of the mechanisms underlying impaired decision-making and behavioral disinhibition in those with AD and related EXT disorders problems. The project attempts to clarify the relevance of these mechanisms for decisions to drink in young adults, and shed light on the potential role that these mechanisms have in the heterogeneity in AD. Such knowledge will be valuable for the prevention and treatment of alcohol problems in young adults. PUBLIC HEALTH RELEVANCE: This is a study of the cognitive and motivational mechanisms in alcohol dependence (AD) and related externalizing (EXT) disorders. The project will provide information about the specific mechanisms that contribute to AD and related EXT disorders, which will be valuable for prevention and treatment efforts. [unreadable] [unreadable] [unreadable]